► The researches on cinema performer have increased in the last years. During the silent era the actor was a central issue of the theorists agenda,…
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▼ The researches on cinema performer have increased in the last years. During the silent era the actor was a central issue of the theorists agenda, but after the Second World War it has been studied almost merely as a sociological or iconographic matter. The actor, still nowadays, strongly conditions the choice of seeing a movie, but the scholars have often preferred to focus on style, authorship, direction and other subjects. My project intends to analyze the difference between the 1910s European performers and the Early cinema actors, but primarily I would give attention to the 1910s and avant-garde performers of the European cinema as distinguish feature in relation to Hollywood cinema. The Italian silent cinema of the 1910 is one of the historical contexts of the analysis, while the 1920s reflection on cinema performing is the theoretical reference to formulate new hypothesis on European silent actor. My work aims also at putting the study of the actor into a perspective including the relation between cinema and the other arts, the stardom and the anthropological matters.
Asta Nielsen has been the first female star of world cinema. Her name is strictly connected with the advent of the long feature film and the introduction of the star system. Asta Nielsen’s international film career started in Germany with the introduction of the Monopolfilm, the monopoly rental system, in late 1910 and continued in many country. Starting from the analysis of the incredible success of Asta Nielsen’s films in the local context of Zürich, considering the presuppositions and consequences of this popularity, also in comparison with other contexts, I will examine the emergence and the strengthening of film actor in Europe as the main component of the cinematic experience since 1910. Experience that should be understood as a particular way with which the cinematographic institution make a film consumable for a spectator. Consequently, my research aims to study the aspects of cinema going, film aesthetic and film reception during 1910s, which involves directly the discovery of film actor and film acting.
Advisors/Committee Members: tutore: E. Dagrada, co-tutore: M. Troehler (Universitaet Zuerich), DAGRADA, ELENA.

► Flowering time regulation has a strong impact on plant life cycle, since it allows plants to flower and to reproduce under environmental permissive conditions. Several…
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▼ Flowering time regulation has a strong impact on plant life cycle, since it allows plants to flower and to reproduce under environmental permissive conditions. Several genes are involved in the regulatory pathways that determine the floral transition step, i.e. the switch from the plant vegetative phase to the reproductive phase and the consequent flower formation and fruit set. Among those genes, SHORT VEGETATIVE PHASE (SVP), a MADS box transcription factor, acts as strong repressor of the so called florigen promoting genes, FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1). Moreover, SVP has been also reported to act as a repressor of flower homeotic gene expression, thus ensuring the correct maintenance of floral meristem identity. Due to the relevance of SVP in both such important plant developmental stages, during my Ph.D. research program I tried to elucidate the molecular mechanisms at the basis of SVP activities. That has been done through different and complementary strategies that had the dual aim to identify SVP protein partners and to move the first steps towards the comprehension of the role of chloroplasts and chloroplast-nucleus signaling pathways in SVP functions.
Co-immunoprecipitation assays followed by Mass Spectrometry analyses have allowed to draw up a list of Arabidopsis putative robust SVP interactors involved, at different levels, in chromatin organization and histone modification. Interestingly, the detailed characterization of the major Arabidopsis trimethyltransferase enzyme, SET DOMAIN GROUP 2 (SDG2), has revealed the existence of an SVP-SDG2 containing protein complex able to regulate the expression of SVP gene at the vegetative and reproductive meristems, by affecting the H3K4 methylation pattern within the first exon of SVP.
Furthermore, our interests on the role of chloroplast-nucleus communication and its possible interactions with the flowering time regulation, have been met through the detailed characterization of two chloroplast-located PENTATRICO-PEPTIDE-REPEAT (PPR) containing proteins, which share three main features: i) they are part of the chloroplast gene expression machinery, ii) they are involved in chloroplast-nucleus communication, iii) they have been reported to be target genes of SVP by ChiP-seq assays.
The detailed characterization of the Arabidopsis PPR proteins, GENOME UNCOUPLED 1 (GUN1) and CHLOROPLAST RNA PROCESSING 1 (AtCRP1), has provided the first preliminary insights into how chloroplast-nucleus signaling mechanisms may enable higher plants to more effectively adapt to the ever-changing internal and external conditions and mitigate detrimental effects to fitness.
Advisors/Committee Members: tutor, supervisor e coordinatore: P. Pesaresi, PESARESI, PAOLO.

► High-order angular correlation functions and their harmonic counterpart, the polyspectra, offer a great opportunity to study the physics of spherical random fields. The best example…
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▼ High-order angular correlation functions and their harmonic counterpart, the polyspectra, offer a great opportunity to study the physics of spherical random fields. The best example of such a field is represented by the Cosmic Microwave Background (CMB) radiation, a relic from the hot phases of our Universe. But even the Large Scale Structure (LSS) as traced by galaxies can be treated in the same way when considering shells of iso-redshift. Both CMB and LSS are the most relevant source of cosmological information available today.
This thesis offers a review of the analytical framework of spherical random distributions and polyspectra together with the now so-called standard cosmological model. The physics of inflation and the evolution of tiny quantum almost Gaussian fluctuations that eventually evolved into both CMB and LSS is also presented in details.
The high-order angular polyspectra considered here are the Bispectrum and the Trispectrum. The former has been applied to LSS simulated data, the latter on CMB simulated data. The results of the analysis show that both of them could be useful in the next future in order to constrain cosmological parameters from real data.
A three-year journey to understand how primordial fluctuations grew in the structures we see today.
Advisors/Committee Members: tutor: D. Maino, E. Sefusatti, coordinatore: F. Ragusa, MAINO, DAVIDE, RAGUSA, FRANCESCO.

► Through a reflection on the notions of form and content originating from Kant’s philosophy, this work offers a new interpretation of British idealism. Its starting…
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▼ Through a reflection on the notions of form and content originating from Kant’s philosophy, this work offers a new interpretation of British idealism. Its starting point consists in recognizing the heterodox character of the idealist doctrines developed in the United Kingdom as a result of the interpretations of the philosophies of Kant and Hegel. In order to achieve this goal, the influence of Kant’s philosophy on the metaphysical proposals of the philosophers on the other side of the English Channel is first discussed. The notions of form and content represent the gateway to criticism, and allow reasoning about the new concepts of experience and object that were proposed in the first Critique. Through to the analysis of Bradley’s logical doctrine of judgment (which is compared to the concept of existence in Kantian philosophy), and of McTaggart’s famous argument about the unreality of time (vastly different from the definitions of the Transcendental Aesthetic), the British idealists’ approach is questioned, for it does not meet Kant’s presuppositions and requirements. This conclusion is also endorsed by the discussion of Stirling’s criticism to transcendental philosophy. However, since Hegel climbed the ladder of critical philosophy, raising his discourse to a level defined as “meta-transcendental”, the suspension of criticism brings to the suspension of Hegelianism as well. The notions of form and content no longer lay in the sphere of transcendental subjectivity: the method of logic in its proceedings, i.e., its immanent connection and necessity as science, is the identity of form and content in the element of pure thought. The analysis shows that the British idealists do not comprehend the significance of Hegel’s absolute philosophy: not only do they lower it to a subjective method, but they also reformulate the principles of dialectic, so that pure thought remains subordinate to the concept of being. Since the genesis of analytical philosophy is commonly regarded as a reaction against idealism, the relevance of these considerations is not limited to their mere historical interest: by refuting the arguments of the German philosophers, analytic philosophy does not undermine those of the British idealists—and vice versa.
Advisors/Committee Members: tutor: S.Turró, PETTOELLO, RENATO.

► Embryogenesis, germination and early phases of seedling growth represent critical phases in the plant life cycle and are probably the most important events in determining…
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▼ Embryogenesis, germination and early phases of seedling growth represent critical phases in the plant life cycle and are probably the most important events in determining the success of an annual plant.
A rapid and robust emergence positively influences the capacity of the plant to take advantage of the favourite environment and to compete with its neighbours. In the perspective of a more sustainable agriculture specific characters are envisaged for a crop seedling, such as the resistance to environmental critical abiotic as well as biotic factors. For these reasons key factors subtending plant developmental process and contributing to the achievement of a productive and robust plant have to be searched inside the genetic network that control embryo and seedling development.
Among the different aspects affecting seedling development the two that will be analysed in this study play an important role also in the interplay with the environment. Hormones are endogenous signals governing seedling growth and architecture establishment but at the same time are able to induce plant response to environmental stress. Wax deposition is required for determining a correct embryo and seedling development, and provides, beside that, a protective barrier that plants produce in their early developmental phases to defend themselves from pathogens as well as from variation in environmental abiotic components, such as temperature and water availability.
Here, we report the characterization of the mutants lilliputian 1-1 (lil1-1) and fused leaves 1-1 (fdl1-1), both ascribable to defective seedling (des) maize mutants.
lilliputian 1-1 (lil1-1) is a monogenic recessive mutant of maize, isolated from an active Mutator (Mu) stock and attributed to the insertion of a Mutator1 element in the first exon of a the gene encoding the BR C-6 oxidase. The enzyme belongs to the superfamily of CYP85A proteins and catalyzes the final steps of brassinosteroid synthesis. lil1-1 mutant exhibits a reproducible phenotype consisting of a large primary root, extremely reduced stature and crinkly leaves. Recently, another dwarf mutant of maize impaired in the same brassinosteroid C-6 oxidase and showing a very similar phenotype of lil1-1 has been characterized and the corresponding gene was termed brasssinosteroid deficient 1 (brd1)
Allelism between the two mutant alleles has been demonstrated in this work. Moreover, it has been observed that the exogenous application of brassinolide to the lil1 mutant seedlings resulted in a partial recovery of the lil1-1 phenotype. This observation is in agreement to what previously observed for brd1-m in maize and other Br-deficient mutants in Arabidopsis, rice and tomato.
Differently from some of these mutants, i.e det2 of Arabidopsis, lil1 genotype does not influence the seed formation and development. It is evident that the comparison between homozygous lil1-1 mutant and Li11-1 wild-type seeds from the same segregating ear did not highlight any difference in weight. In addition, F2 progeny ears obtained from F1…
Advisors/Committee Members: supervisor: G. Consonni, co-supervisor: F. F. Nocito, CONSONNI, GABRIELLA, NOCITO, FABIO FRANCESCO.

► The Haspin gene encodes an atypical serine/threonine mitotic kinase first discovered in mouse spermatocytes and preferentially expressed in tissues with a high rate of proliferating…
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▼ The Haspin gene encodes an atypical serine/threonine mitotic kinase first discovered in mouse spermatocytes and preferentially expressed in tissues with a high rate of proliferating cells. Haspin acts at metaphase by phosphorylating threonine 3 of histone H3 (H3Thr3PH) and this modification allows the recruitment of the chromosomal passenger complex, a key factor required to orchestrate different steps of mitosis. In human cells, HASPIN depletion causes a decrease in H3Thr3 levels, resulting in premature loss of sister chromatid cohesion and in defects in chromosome alignment at metaphase. Haspin has been found in all eukaryotic organisms; however, up to know, its role during animal embryonic development has never been investigated. We decided to investigate its function and expression during zebrafish embryonic development and, to this aim, we took advantage of a morpholino (MO)-mediated knockdown approach and of the CRISPR-Cas9 knockout strategy.
We identified and cloned the zebrafish haspin ortholog, together with a previously unknown splicing isoform, and we clarified its expression pattern during embryogenesis and in some adult tissues. We demonstrated a relevant maternal contribution for the haspin transcript and important levels of zygotic expression in tissues with a high rate of proliferating cells, such as the developing brain and hematopoietic tissues. We also detected haspin transcript in the adult gonads and found that its expression is significantly switched on after injury during adult fin tissue regeneration.
Interestingly, after Haspin functional inactivation using two different MOs, a translation blocking (ATG MO) and a splicing one, we demonstrated that Haspin is involved in H3Thr3PH also in zebrafish. Moreover, microinjection of the haspin ATG MO results in high embryo mortality and severe defects during epiboly stages, indicating important alterations in cellular rearrangements and movements.
A haspin stable mutant line was generated by using the CRISPR-Cas9 technology: we isolated three different mutant haspin alleles, all causing the formation of premature stop codons. Although they do not show evident phenotypic alterations during embryogenesis, embryos carrying a homozygous genotype for these mutations are not able to reach the adulthood stage, showing a high rate of mortality in the first three weeks of larval development, indicating that Haspin is fundamental for larval survival and growth.
To conclude, we clarified various aspects of haspin expression pattern during zebrafish development and in adult organs. Even though we were not able yet to unambiguously define the phenotypic effect of Haspin functional inactivation by using a MO-mediated approach, we paved the way for the analysis of the effect of a complete haspin gene knockout during zebrafish development by generating a haspin stable KO line and by showing that this null mutant allele significantly affects larval survival and growth.
Advisors/Committee Members: tutor: Prof. Paolo Plevani, PLEVANI, PAOLO.

► This thesis analyses the political and institutional development of the populus of the Umbrian city-states in connection with the municipal documentary activity in the second…
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▼ This thesis analyses the political and institutional development of the populus of the Umbrian city-states in connection with the municipal documentary activity in the second half of the thirteenth century. The aim of the research was to identify the initiatives explicitly promoted by the populus in the field of production and documentation management.
Umbria was chosen as field of study because of its historical and geographical context, characterized by a particularly high density of small and medium city-states and a remarkably rich municipal documentation. This research has focused in particular on the city-states of Assisi, Gubbio, Orvieto, Perugia, Spoleto and Todi, all presenting different characteristics, such as territorial extension, incisiveness of popular regimes, relevance in historiography field. In this area municipal records directly related to an offitium of the populus’ institutional bodies have been identified and analysed.
The gradual affirmation of the populus in the Umbrian city-states government as well as the many documentary initiatives specifically commissioned by popular magistrates are characterized by the extreme variety of the solutions adopted both in the institutional field and in the municipal documentation management. Finally re-writing of certain acts, operated by the offitium capitanei populi, seems to indicate a direct interference and a control of the capitaneus in preforming certain tasks by other municipal offitiales.
Advisors/Committee Members: tutor: Paolo Grillo (Università degli studi di Milano), Cristina Carbonetti Vendittelli (Università degli studi di Roma Tor Vergata), coordinatore del dottorato: Vittorio Criscuolo, GRILLO, PAOLO, CRISCUOLO, VITTORIO.

► Mediterranean region is one of world’s best explored areas in terms of ornithological research and it is considered a main biodiversity hotspot for the Western…
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▼ Mediterranean region is one of world’s best explored areas in terms of ornithological research and it
is considered a main biodiversity hotspot for the Western Palearctic (Myers et al. 2000), especially
because it played a fundamental role in the divergence and speciation processes for many taxa, due
to dynamics linked mainly to glaciations and salinity crises (Hewitt 1996; Taberlet et al. 1998).
Most taxonomical research in ornithology carried on within this region has been based on
anatomical and morphological differentiation of populations; this could have led to underestimating
the real degree of divergence occurring in some morphologically cryptic populations in the region.
We here analyse genetic divergence in two Sylvia (Aves: Sylviidae) species, formerly suspected of
hiding complexes of cryptic sister species.
We demonstrate the existence of complete molecular diagnosability and strong patterns of
structuration of molecular variability in mitochondrial and nuclear markers for two taxa, which we
propose to elevate to the rank of Confirmed Candidate Species (Galimberti et al. 2012): Sylvia
[sarda] balearica and western Sylvia [cantillans] cantillans.
We simultaneously urge the need to properly re-evaluate conservation status and policies for at least
Sylvia [sarda] balearica, endemic to only a small archipelago.
Molecular identification of migrating and wintering individuals of Sylvia [cantillans] allowed us to
gather the first certain data about the wintering areas of single taxon of the species complex and to
highlight a pattern of great dynamism in their yearly trajectories. We suggest expanding our
preliminary research by coupling a more capillary distribution of ringing efforts in Northern and
Central Africa with molecular identifications of trapped individuals.
Advisors/Committee Members: tutor: D. Rubolini, coordinator: C. Bandi, RUBOLINI, DIEGO, BANDI, CLAUDIO.

► Peripheral neuropathies are a heterogeneous group of pathologies with a high prevalence worldwide, which are characterized by alterations of peripheral nerves structure and function. Their…
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▼ Peripheral neuropathies are a heterogeneous group of pathologies with a high prevalence worldwide, which are characterized by alterations of peripheral nerves structure and function. Their treatment is currently a challenge for clinicians. Indeed, even if continuous progresses are made in the study of the basic mechanisms underlying these pathologies, etiology is still unknown in a significant number of cases. Different compounds, such as growth factors, adhesion proteins, neurotransmitters, enzymes, peptides and neuroactive steroids, have been proposed to play important roles in the patho-physiology of the peripheral nervous system. Therefore, most of the research is addressed to identify the molecules that might represent the more promising therapy for this set of pathologies.
This thesis focuses on some aspects of the patho-physiological role of the GABAergic system and neuroactive steroids in the peripheral nervous system.
Several papers in literature strongly support the hypothesis that they are both present and active in the peripheral nervous system, in particular in Schwann cells, the myelinating cells of the peripheral nervous system. These cells are indeed able to synthesize GABA and neuroactive steroids and express both the ionotropic GABA-A and the metabotropic GABA-B receptor. In order to deepen the knowledge on this topic, four research lines were pursued in my PhD program and are described in this thesis. The first line regarded the analysis of the effects of specific GABA-B ligands on nerve regeneration in a model of neuropathic pain caused by nerve ligation. These studies showed that the specific GABA-B antagonist CGP56433 was able to recover some morphological, functional and biochemical parameters in peripheral nerves. Surprisingly, some of these effects were potentiated by the co-treatment with GABA-B specific agonist baclofen, suggesting the co-activation of possible central and peripheral mechanisms. The second research line regarded the analysis of different GABA-A subunits in dorsal root ganglia (DRG) neurons of a model of conditional knockout mice, in which the GABA-B1 receptor is specifically deleted in Schwann cells. The results showed a modulation of different GABA-A subunits, pointing to a down-regulation of GABA-A receptors, mainly regarding the synaptic ones. This evidence may contribute to understand some of the alterations that were previously observed in this conditional knockout mouse model. The third research line dealt with the study of the modulation of protein kinase C-type ε (PKCε), an important neuropathic pain mediator, and its possible cross-talk with the GABA-A receptor and the neuroactive steroid allopregnanolone. The results showed that allopregnanolone down-modulates PKCε expression in Schwann cells, but the direct treatment on DRG neurons did not lead to any significant effect. However, Schwann cells conditioned medium was able to induce a significant up-regulation of PKCε gene expression in DRG neurons. Also the membrane expression of PKCε phosphorylated form…
Advisors/Committee Members: tutor: V. Magnaghi, coordinatore: C. Sforza, MAGNAGHI, VALERIO, SFORZA, CHIARELLA.

Castelnovo, L. (2017). MOLECULAR BASIS FOR THE DEVELOPMENT OF INNOVATIVE THERAPIES FOR PERIPHERAL NEUROPATHIES TREATMENT: ROLE AND CROSS-REGULATION OF THE GABAERGIC SYSTEM AND NEUROACTIVE STEROIDS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/465187

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Castelnovo, L.F.. “MOLECULAR BASIS FOR THE DEVELOPMENT OF INNOVATIVE THERAPIES FOR PERIPHERAL NEUROPATHIES TREATMENT: ROLE AND CROSS-REGULATION OF THE GABAERGIC SYSTEM AND NEUROACTIVE STEROIDS.” 2017. Thesis, Università degli Studi di Milano. Accessed March 19, 2018.
http://hdl.handle.net/2434/465187.

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Castelnovo, L.F.. “MOLECULAR BASIS FOR THE DEVELOPMENT OF INNOVATIVE THERAPIES FOR PERIPHERAL NEUROPATHIES TREATMENT: ROLE AND CROSS-REGULATION OF THE GABAERGIC SYSTEM AND NEUROACTIVE STEROIDS.” 2017. Web. 19 Mar 2018.

Vancouver:

Castelnovo L. MOLECULAR BASIS FOR THE DEVELOPMENT OF INNOVATIVE THERAPIES FOR PERIPHERAL NEUROPATHIES TREATMENT: ROLE AND CROSS-REGULATION OF THE GABAERGIC SYSTEM AND NEUROACTIVE STEROIDS. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2018 Mar 19].
Available from: http://hdl.handle.net/2434/465187.

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Castelnovo L. MOLECULAR BASIS FOR THE DEVELOPMENT OF INNOVATIVE THERAPIES FOR PERIPHERAL NEUROPATHIES TREATMENT: ROLE AND CROSS-REGULATION OF THE GABAERGIC SYSTEM AND NEUROACTIVE STEROIDS. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/465187

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

12.
P. Songia.
OSTEOPROTEGERIN AS A NEW POSSIBLE PLAYER IN MITRAL VALVE PROLAPSE WITH SEVERE REGURGITATION: FROM IN VITRO TO HUMAN STUDIES.

Songia, P. (2017). OSTEOPROTEGERIN AS A NEW POSSIBLE PLAYER IN MITRAL VALVE PROLAPSE WITH SEVERE REGURGITATION: FROM IN VITRO TO HUMAN STUDIES. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/468430

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Songia, P.. “OSTEOPROTEGERIN AS A NEW POSSIBLE PLAYER IN MITRAL VALVE PROLAPSE WITH SEVERE REGURGITATION: FROM IN VITRO TO HUMAN STUDIES.” 2017. Thesis, Università degli Studi di Milano. Accessed March 19, 2018.
http://hdl.handle.net/2434/468430.

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Songia, P.. “OSTEOPROTEGERIN AS A NEW POSSIBLE PLAYER IN MITRAL VALVE PROLAPSE WITH SEVERE REGURGITATION: FROM IN VITRO TO HUMAN STUDIES.” 2017. Web. 19 Mar 2018.

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Songia P. OSTEOPROTEGERIN AS A NEW POSSIBLE PLAYER IN MITRAL VALVE PROLAPSE WITH SEVERE REGURGITATION: FROM IN VITRO TO HUMAN STUDIES. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/468430

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

► Lung cancer is the leading cause of cancer-related deaths worldwide and cigarette smoking is related to 90% of all deaths due to lung cancer. Tobacco…
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▼ Lung cancer is the leading cause of cancer-related deaths worldwide and cigarette smoking is related to 90% of all deaths due to lung cancer.
Tobacco smoke contains many classes of carcinogens and, although nicotine, the addictive and most active component of tobacco smoke, is unable to initiate tumourigenesis in humans and rodents, it promotes tumour growth and metastasis by inducing cell-cycle progression, cell migration, angiogenesis and the evasion of apoptosis in a variety of systems.
Nicotine and its metabolites are highly lipophilic compounds that bind and activate a family of ligand-gated cation channels (the neuronal nicotinic acetylcholine receptors, nAChRs) that are widely expressed in the central and peripheral nervous systems.
Over the last few decades, the extra-neuronal localisation of nAChRs has been demonstrated in a large number of cell types including endothelial cells, glia, immune cells, lung tissue and cancer cells, indicating that they might have functions well beyond simple neurotransmission.
Recent studies have shown that most of the tumour-promoting effects of nicotine are primarily due to the binding and the activation of nAChRs, which lead to downstream intracellular signalling cascades. However, identifying the receptor subtypes expressed in lung tumour cells and their signalling pathways is still in its early stage.
For these reasons, we investigated the pathophysiological role of nAChRs in lung cancer cells.
We found that different non-small cell lung cancer (NSCLC) cells express distinctive nicotinic receptor subtypes and that this variety affects nicotine-induced proliferation and migration. In the A549 adenocarcinoma cell line, nAChRs containing the α7, α9 and α5 subunits regulate not only the nicotine-induced cell proliferation and migration but also the activation of anti-apoptotic and proliferative pathways. Blocking nAChRs containing the α7 or α9 or α5 subunits with specific toxins or silencing their expression by means of subunit-specific siRNAs abolishes the nicotine-induced proliferation, migration and signalling.
Prompted by these results, we also studied oxystylbene compounds previously characterised by our group and started to syntehesise some new oxystylbene/resveratrol derivatives with specific modifications. We found that these 4-oxystilbene derivates act on both α7 and α9-containing receptors and block NSCLC cell proliferation and viability in a dose-dependent manner.
These results highlight the pathophysiological role of specific nAChR subtypes in promoting NSCLC cell growth and migration and raise the possibility of targeting them in order to treat tobacco related cancer.
Advisors/Committee Members: tutor: A. E. Panerai, co-tuor: C. Gotti, coordinatore del dottorato: A. Corsini, PANERAI, ALBERTO EMILIO, CORSINI, ALBERTO.

► In the last years, evidence accumulated showing a direct connection between brain inflammation and neurodevelopmental disorders such as autism and schizophrenia. Epilepsy and seizures episodes,…
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▼ In the last years, evidence accumulated showing a direct connection between brain inflammation and neurodevelopmental disorders such as autism and schizophrenia. Epilepsy and seizures episodes, in particular, are associated to enhanced brain inflammation, while the activation of the immune response consequent to infections strongly increases the risk of seizures.
By using the Poly I:C (polyinosinic-polycytidylic acid) mouse model of maternal immune activation (MIA), we demonstrated that a single administration at gestational day 9 (GD9) is able to affect the glutamate-GABA equilibrium in the offspring through a long-lasting deregulation of the chloride transporter KCC2 at cortical level, resulting in an alteration of the hyperpolarizing action of GABA, which endures at mature stages, as highlighted by the increased seizure susceptibility. Furthermore, mice injected with Poly I:C during adult life show no differences in susceptibility to kainate-induced seizures respect to control mice, thus providing the evidence that the increased susceptibility to seizures following prenatal Poly I:C exposure is the consequence of a neurodevelopmental process. We also provide the proof-of-concept that KCC2 expression abnormality and its deleterious physiological consequences can be prevented by dietary maternal supplementation with MgSO4, already known to reduce inflammation at the maternal-fetal interface. Notably, the increased binding of the two master regulators of neuronal genes expression, REST and MeCP2, on KCC2 promoter, suggests a possible epigenetic mechanism involved in the regulation of KCC2 expression following inflammation in the mother. Thus, maternal immune activation, through pro-inflammatory cytokines, may lead to epigenetic modifications responsible for KCC2 dysregulation and the consequent pathological outcomes, as suggested also by in vitro experiments.
Advisors/Committee Members: co-tutor: E. Menna, tutor: F. Scaglione, coordinatore: A. Corsini, SCAGLIONE, FRANCESCO, CORSINI, ALBERTO.

► Religious change in Europe continues to be a controversial topic. The main disputes regard if and how Europe is experiencing processes of secularization and how…
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▼ Religious change in Europe continues to be a controversial topic. The main disputes regard if and how Europe is experiencing processes of secularization and how these processes can be explained. On the one hand, there are basically three different theories which strongly compete. Secularization theorists declare that religiosity in Europe is declining in all its dimensions. Individualization theorists declare that religion is changing instead from institutionalized forms to more individualized and intimate ones. Finally, adherents of the economic market approach prompt that religiosity is all about the ability of the churches to stimulate and attract believers. On the other hand, the link between modernization and secularization is often presented as the causal mechanism underneath religious change. Among this literature, Norris and Inglehart’s insecurity theory poses that processes of modernization and human development have increased the human security thus reducing the need for religion. This theory is based on the idea that religion can work as reassurance for conditions of insecurity or for life-threatening events. The present work tests this claim. After giving a comprehensive overview of the three main theoretical approaches to religious change (chapter 2), of the use of religion as coping strategy (chapter 3) and of the main methodological issues that need to be faced (chapter 4), I describe European religiosity and analyze possible processes of religious change. To do so, I focus on different dimensions of religiosity and I consider cohort replacement as the main mechanism to assess this change (chapter 5). It emerges that Practice is declining in all European countries, but religious self-definition and especially belief show a U-shaped trend for Orthodox countries. Given this peculiarity, I devote an entire chapter (chapter 6) to its exploration. After doing that, I explicitly deal with insecurity theory. To do so, I propose a multiple response multilevel model (EVS data) on European Christian countries (chapter 7) which tackles the association between individual as well as contextual insecurity and individual religiosity. Results show that personal religiosity is weakly associated only with widowhood at the individual level but more strongly associated with economic inequalities and welfare spending at the country level. Chapter 8 goes deeper in the investigation of the relation between individual insecurity and religiosity. By mean of two fixed-effect panel models for Germany (SOEP data) and UK (BHPS + Understanding society data) I am able to explicitly test the hypothesis that a worsening of individual condition can foster an increase of religiosity. Results clearly show that such hypothesis applies only and little for widowhood. Hence, the case of Europe suggests that individual insecurity alone does not suit for a comprehensive sociological theory of religious change. It should be better integrated with other theories, e.g. the increase of education and the failure of religious transmission, to…
Advisors/Committee Members: supervisor: M. Maraffi, co-supervisor: F. Biolcati Rinaldi, phd director: M. Cardano, MARAFFI, MARCO, MARAFFI, MARCO, BIOLCATI RINALDI, FERRUCCIO, Cardano, Mario.

Predictive Molecular Profiles of the Metastatic Potential of Urothelial Carcinoma of the Bladder Stage pT1 or Greater
Introduction: Recent data from genomic analysis of bladder tumors have identified subgroups with different aggressiveness patterns and chemotherapy response profiles. The aim of our study was to identify molecular markers that can be used in clinical practice, to predict the evolution of these tumors in order to personalize their management.
Materials and Methods: DNAs extracted from 54 solid tumors and 50 urine samples from patients with bladder cancer were hybridized on the BCA-oligo CGH (Comparative Genome Hybridization) chip. TMAs (Tissue Micro Array) from 140 paraffine-embedded tissues of primary and metastatic tumors, were analyzed in immunohistochemistry with antibodies directed against proteins involved in DNA stability, cell proliferation and the definition of basal or luminal subgroup. Correlations with clinical data were sought at all levels of analysis.
Results: The number of chromosomal alterations increased significantly with the tumor stage. In addition, the distribution of these alterations was consistent between the DNAs extracted from tumor tissue and those from urinary samples. If no immunohistochemical marker differentiated…

► Present-day cosmology is experiencing a rather exciting season, as many observations of unprecedented quality either have recently been performed or are just about to be…
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▼ Present-day cosmology is experiencing a rather exciting season, as many observations of unprecedented quality either have recently been performed or are just about to be carried out. In this framework, long-standing unsolved questions, such as the nature and dynamics of cold dark matter and dark energy, the laws of gravity on cosmological scales, and the detailed physics of gravitational collapse and galaxy formation, might finally be assessed and hopefully find some answers. However, to maximally extract information from such copious and precise data, theoretical modeling must join the effort and push predictions to higher levels of accuracy.
In the present thesis, I investigate a number of aspects regarding the role of massive neutrinos in cosmology, considering in particular their effects on the Large Scale Structure of the universe. The presence of massive neutrinos leaves its trace on many cosmological observables, requiring us to carefully account for their effects in order not to introduce systematic errors in our theories, but also allowing us to set constraints on quantities such as the number of neutrino species, their total mass and mass hierarchy. For this reason, the study of cosmological neutrinos is not only encompassed within the boundaries of cosmology, but reaches out to fundamental physics.
In the first part of my work, I present a new method to set the initial conditions for cosmological simulations that include massive neutrinos. I then move to the study of the clustering ratio (a cosmological probe that quantifies the clustering properties of the galaxy distribution) in the presence of neutrinos, assessing its constraining power using both current data (from SDSS) and a forecast of a Euclid-like survey. Finally I study the possible degeneracies between neutrino effects and the parameters introduced to account for the galaxy-matter bias in some state-of-the art models.
Advisors/Committee Members: supervisors: Julien Bel, D. Maino, internal supervisor: D, Maino, coordinatore: F. Ragusa, MAINO, DAVIDE, RAGUSA, FRANCESCO.

▼ This thesis completes my work as doctoral student of the Scuola di Dottorato in Fisica, Astrofisica e Fisica Applicata at the Università degli Studi di Milano that has been carried out, starting in November 2014, mostly at the Laboratorio TASC of IOM-CNR in the premises of the Elettra - Sincrotrone Trieste and [email protected] infrastructures, in the framework of the NFFA and APE-beamline facilites, as well as by accessing international large scale infrastructures and laboratories.
The activity has addressed the development of experimental methodologies and novel instrumentation oriented to the study of the dynamical properties of highly correlated materials after high energy excitation. The science programme has been carried out by exploiting ultrafast femtosecond probes from the optical regime (Ti-Sa lasers, fibre laser oscillators) to the extreme UV-soft X rays at FERMI, to the picosecond hard X-rays from the SPring-8 and Diamond synchrotron radiation source. The sample synthesis of correlated oxides and its characterization has been performed within the NFFA facility and APE-group collaboration in Trieste as well as the design and construction of the all new laser High Harmonic Generation beam line NFFA-SPRINT and its end station for time resolved vectorial electron spin polarimetry.
This report concentrates on the main scientific concern of my work that has been the relaxation of external perturbations in a correlated electron material both in the time and space domain.
I have employed Photoelectron Spectroscopy (PES) mostly in the Hard X-ray regime (HAXPES), pushing the boundaries of its application to achieve a coherent perspective. The material I have mainly focused on is La0.67Sr0.33MnO3 (LSMO), of high interest for spintronics. This system is prototypical, yielding the highest simplicity in the class of transition metal oxides.
In the spatial investigation, I have controlled with high precision the PES probing depth and I have observed the evolution of one spectral feature. I have identified it as probe of electronic hybridization and long-range ordering. I have studied LSMO films of 40 nm in three substrate-induced strain states (1% tensile in-plane, relaxed, 1% compressive in-plane) and a 18 nm film of (Ga,Mn)As (GMA), a well-studied diluted magnetic semiconductor. I have found that the electronic properties to be modified at significant distances from the surface, 4 nm for LSMO and 1.2 nm for GMA, while strain had no detectable effects.
In the temporal study, I have employed HAXPES in pump-probe mode (TR-HAXPES) to observe the evolution of the electronic structure after intense optical excitation. A detailed dynamical characterization with optical techniques has allowed me to identify the characteristic time of the collapse of long-range magnetic order to be significantly longer than the one of elemental transition metals. I have ascribed this effect to the half-metallic character of LSMO. With TR-HAXPES I have observed that the whole electronic band-structure evolution is bottlenecked by the slow…
Advisors/Committee Members: supervisor: G. Rossi, co-supervisor: G. Panccione, coordinatore: M. Bersanelli, ROSSI, GIORGIO, ROSSI, GIORGIO, BERSANELLI, MARCO RINALDO FEDELE.

► The work presented in this manuscript is based on the proton-proton collision data from the Large Hadron Collider at a centre-of-mass energy of 13 TeV…
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▼ The work presented in this manuscript is based on the proton-proton collision data from the Large Hadron Collider at a centre-of-mass energy of 13 TeV recorded by the ATLAS detector in 2015 and 2016.
The research program of the ATLAS experiment includes the precise measurement of the parameters of the Standard Model (SM) and the search for signals of physics beyond the SM. Both these approaches are pursued in this thesis, which presents two different analyses.
The first one is the measurement of the Higgs boson mass in the di-photon decay channel. The measured value of the mass is (125.11 ± 0.42) GeV. Its combination with a similar measurement in the four lepton Higgs boson decay final state is presented. The value of the Higgs boson mass obtained from the combined measurement is (124.98 ± 0.28) GeV.
The second one is the search for production of supersymmetric particles (gluinos, squarks or winos) in a final state containing two photons and missing transverse momentum. No significant excess with respect to the SM background is observed and lower limits on the gluino, squark and wino masses are set in the context of a generalised model of gauge-mediated supersymmetry breaking with a bino-like next-to-lightest supersymmetric particle.
Finally, ATLAS detector performance studies (electron and photon energy calibration and measurement of the photon->electron misidentification probability), which are key ingredients for the two analyses presented before, are also performed and described.
Advisors/Committee Members: supervisor: L. Carminati, G. Marchiori, CARMINATI, LEONARDO CARLO.

Manzoni, S. (2017). PHYSICS WITH PHOTONS WITH THE ATLAS RUN 2 DATA: CALIBRATION AND IDENTIFICATION, MEASUREMENT OF THE HIGGS BOSON MASS AND SEARCH FOR SUPERSYMMETRY IN DI-PHOTON FINAL STATE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/534368

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Manzoni, S.. “PHYSICS WITH PHOTONS WITH THE ATLAS RUN 2 DATA: CALIBRATION AND IDENTIFICATION, MEASUREMENT OF THE HIGGS BOSON MASS AND SEARCH FOR SUPERSYMMETRY IN DI-PHOTON FINAL STATE.” 2017. Thesis, Università degli Studi di Milano. Accessed March 19, 2018.
http://hdl.handle.net/2434/534368.

Note: this citation may be lacking information needed for this citation format:Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Manzoni, S.. “PHYSICS WITH PHOTONS WITH THE ATLAS RUN 2 DATA: CALIBRATION AND IDENTIFICATION, MEASUREMENT OF THE HIGGS BOSON MASS AND SEARCH FOR SUPERSYMMETRY IN DI-PHOTON FINAL STATE.” 2017. Web. 19 Mar 2018.

▼ Gorgonzola is a blue-veined, mould-ripened cheese, made from pasteurized cow’s milk inoculated with starter cultures (Streptococcus thermophilus and Lactobacillus delbrueckii), along with Saccharomyces cerevisiae and Penicillium roqueforti, the main responsible of the aroma and flavour of the cheese at the end of ripening. For this reason, monitoring the fungal growth and unravel the microbial dynamics during the ripening process is crucial. Traditional methods based on colony forming unit (CFU) along with alternatives (ergosterol, dry weight, spores counting) are not suitable for hyphal filaments quantification in the cheese matrix. Here we monitored and compared the P. roqueforti development between two Gorgonzola productions from two different years and the same plant, by means of a qPCR assay, mass spectrometry-based chemical analysis and an assay with a glutamate-sensitive luminescent biosensor for the evaluation of proteolysis. qPCR assay was based on a species-specific primer set targeted on ari1 gene. This assay allowed the monitoring of P. roqueforti development during cheese ripening. The lipolysis and proteolysis cheese profiles obtained by mass-spectrometry and luminometric analysis were in good agreement with the qPCR data, revealing that the most relevant blooming of the mould occurs after 20 days of ripening, and that the most recent production had a lower amount of fungal mycelium produced and a lower enzymatic activity, thus affecting the final product quality. The metabolic analysis on sugars consumption revealed the importance of galactose degradation on the final product quality. The analytical methods here described are useful for a rapid evaluation of the maturation process and the quality of blue-cheeses.
Advisors/Committee Members: tutor: D. Mora, coordinator: F. Bonomi, MORA, DIEGO, BONOMI, FRANCESCO.

▼ Bisphosphonates (BP), syntetic analogues of inorganic pyrophosphate are able to inhibit the osteoclastic activity, quickly bonding the mineral component of bone structure. BPs are excreted unchanged by glomerul filtration in urine, except for a very small fraction, which is excreted in the bile. After they are absorbed by the bone, BPs are released from hydroxyapatite during bone resorption, taken-up by osteoclasts, and then they are released again when the bone is resorbed. This explain the very slow and long elimination of all BPs from skeleton [ Drake MT et al., 2010]. Consequently, a long time accumulation in the osseous tissue has benn speculated. Nevertheless, a direct method to measure these drugs in the human bone tissue is not available in literature. In man, the concentration of BPs stored in bone is estimated on basis of administred dose and quantity of drugs detected in serum and, most of all, in urine. Considering the complete absence of information on this topic, the aim of this study is to investigate the presence of BPs in bone sequestra (surgically removed or naturally exfoliated) in patients with osteonecrosis of the jaw caused byBPs (BRONJ), followed by the Oral Pathology Unit of the San Paolo Hospital, University of Milan, and in Dental Unit of Papa Giovanni Paolo XXIII Hospital of Bergamo.
Advisors/Committee Members: supervisor: G. Lodi, tutor: E. Varoni, LODI, GIOVANNI, LODI, GIOVANNI.

▼ This thesis concerns the study of fourth-order elliptic boundary value problems and, in particular, qualitative properties of solutions. Such problems arise in various fields, from plate theory to conformal geometry and, compared to their second-order counterparts, they present intrinsic difficulties, mainly due to the lack of the maximum principle.
In the first part of the thesis, we study the positivity of solutions in case of Steklov boundary conditions, which are intermediate between Dirichlet and Navier boundary conditions. They naturally appear in the study of the minimizers of the Kirchhoff-Love functional, which represents the energy of a hinged thin and loaded plate in dependence of a parameter. We establish sufficient conditions on the domain to obtain the positivity of the minimizers of the functional. Then, for such domains, we study a generalized version of the functional. Using variational techniques, we investigate existence and positivity of the ground states, as well as their asymptotic behaviour for the relevant values of the parameter.
In the second part of the thesis we establish uniform a-priori bounds for a class of fourth-order semilinear problems in dimension 4 with exponential nonlinearities. We considered both Dirichlet and Navier boundary conditions and we suppose our nonlinearities positive and subcritical. Our arguments combine uniform estimates near the boundary and a blow-up analysis. Finally, by means of the degree theory, we obtain the existence of a positive solution.
Advisors/Committee Members: tutor: F. Hamel, E. Parini, B. Ruf, coordinatore Unimi: V. Mastropietro.

► The present study proposes a clarification on the molecular mechanism by which ganglioside GM1 promotes neurodifferentiation, demonstrating in vitro that neurotrophic functions are exerted by…
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▼ The present study proposes a clarification on the molecular mechanism by which ganglioside GM1 promotes neurodifferentiation, demonstrating in vitro that neurotrophic functions are exerted by an interaction between the oligosaccharide portion (OligoGM1) and an extracellular domain of TrkA receptor.
Similarly to the entire molecule, the oligosaccharide portion of ganglioside GM1, rather than ceramide, is responsible for neurodifferentiation by augmenting neurite elongation and by increasing the expression of neurofilament proteins in mouse neuroblastoma cell line Neuro2a (N2a).
Conversely, the single components of OligoGM1 (asialo-OligoGM1, OligoGM2, OligoGM3, sialic acid or galactose) are not able to induce a neuro-like morphology. The neurodifferentiative effect is exerted instead by fucosyl-OligoGM1.
Contrarily to GM1, exogenous OligoGM1 never integrates in the plasma membrane composition and does not belong to the intracellular metabolism: the unique interaction with N2a is characterized by a weak non-covalent association to the plasma membrane that suggests the existence of an OligoGM1-stimulated target on the cell surface.
In fact, the neurotrophic properties of GM1 oligosaccharide are exerted by activating TrkA receptor and the following cascade leading to neurodifferentiation event.
The second part of this study elucidates the interaction between GM1 and TrkA, revealing a direct association of OligoGM1 to an extracellular domain of the receptor.
Photolabeling experiments, performed employing nitrogen azide radiolabeled GM1 derivatives, show a direct association of the oligosaccharide chain to TrkA.
Moreover, a bioinformatics study reveals that OligoGM1 fits perfectly in a pocket of the TrkA-NGF complex, stabilizing and favoring their intermolecular interactions as revealed by the increase in energy associated to the new complex TrkA-NGF-OligoGM1. A precise molecular recognition process between OligoGM1 and a specific extracellular domain of the TrkA receptor is supposed. According to the weak association of OligoGM1 to the cell surface, no covalent bounds between OligoGM1 and TrkA-NGF complex were found.
For the first time the molecular mechanism by which GM1 exerts its neurodifferentiative potential was identified, finding out a direct interaction between the oligosaccharide portion and an extracellular domain of TrkA receptor responsible for enhancing the signal transduction related to the neurodifferentiation pathway.
Advisors/Committee Members: docente guida: S. Sonnino, tutor: E. Chiricozzi, coordinatore: S. Sonnino, SONNINO, SANDRO.

► Mesenchymal stem cells (MSC) are multipotent progenitor cells with self-renewable capacity and the potential to differentiate into various cell types, especially of the mesodermal lineages.…
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▼ Mesenchymal stem cells (MSC) are multipotent progenitor cells with self-renewable capacity and the potential to differentiate into various cell types, especially of the mesodermal lineages. They have immunomodulatory properties and, in particular, when exposed to pro-inflamatory cytokines, they acquire immunosuppressive and anti-inflammatory properties due in part to an array of soluble mediators. These cells can be used for a potential therapeutic application but, until now, a thourough characterization of pro-inflammatory primed MSC secretome is still lacking, because its characterization in vivo is very difficult. So, a commonly used approach is the analysis of media conditioned (CM) by cells in culture. The aim of this investigation is the proteomic characterization of bone marrow derived cultured MSC secretome following stimulation with pro-inflammatory cytokines, using two different models: mouse and human patients. This is a fundamental step in order to clarify the mechanism of MSC activity and to design strategies to modulate their properties for rational therapy design and improvement of existing therapies. The proteomic analysis of human MSC-CM and mouse MSC-CM confirms that exposure to pro-inflammatory cytokines results in significantly higher secretion of a number of immunomodulatory and angiogenesis-related proteins by MSC from both species. Notably, 62% of the proteins identified in st hMSC-CM were also identified in st mMSC-CM, clearly highlighting the existence of a common signature in the secretome of human and mouse MSC. However, although human and mouse MSC show a similar proteomic signature in response to stimulation by pro-inflammatory cytokines, our data indicate that they may induce different biological responses. In both species, several up-regulated proteins are associated with angiogenesis, a process that requires degradation of the vascular basement membrane and remodelling of the extracellular matrix to allow endothelial cells migration and invasion into the surrounding tissue. This is possible through the action of matrix metalloproteinases (MMPs) that degrade both matrix and non-matrix proteins and have central roles. So, the balance between MMPs and their natural inhibitors, the TIMPs, is critical for extracellular matrix remodelling and angiogenesis. Using both in vitro and in vivo assays, we identified the metalloproteinase inhibitor TIMP-1 as the molecule responsible for the anti-angiogenic effects of MSC. By identifying TIMP-1 as a critical effector of the anti-inflammatory properties of MSC, and by observing its anti-angiogenic role, both in mouse and in human, we can confirm the important role of TIMP-1 as key secreted molecule targeting endothelial cells. The identification of TIMP-1 as potential effector molecule responsible for the anti –angiogenic properties of MSC, both in mouse and in human, allow to confirm that MSC exert specific effect by secretion of a broad range of bioactive molecules and allow to design pre-clinical experiments and clinical trials, with the aim of…
Advisors/Committee Members: tutor: G. Tedeschi, coordinatore: S. Sonnino, SONNINO, SANDRO.

► I started my Ph.D. at the Physics Department of the Universit`a degli Studi di Milano in November 2014. I carried out my research activity within…
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▼ I started my Ph.D. at the Physics Department of the Universit`a degli Studi di Milano in November 2014. I carried out my research activity within the ATLAS experiment at the Large Hadron Collider (LHC) at CERN, mainly focusing on the upgrade of the ATLAS Liquid Argon (LAr) electromagnetic calorimeter Phase-I trigger electronics. The main topic of my doctoral project is the implementation of VHDL firmware for the Field Programmable Gate Arrays (FPGAs) of the new calorimeter trigger electronics.
I spent the first of the three Ph.D. years working in Milano and the last two years at CERN, supported by a contract awarded from the ATLAS LAr calorimeter group. During the three years of activity, I contributed to the development and maintenance of the FPGA readout firmware for the LAr Phase-I demonstrator system, set up and installed in the ATLAS detector during summer 2014. The purpose of the system is to validate the energy reconstruction and collect real collision data using a pre-prototype of the future front-end and back-end electronics. In addition, I joined the group working on the firmware development for the FPGAs of the new Phase-I back-end boards. I was asked to be in charge of the firmware module for decoding the Timing Trigger and Control (TTC) signals coming from the LHC central trigger processor.
Advisors/Committee Members: supervisor: V. Liberali, F. Tartarelli, coordinatore: F. Ragusa, referee: M. Lisboa Leite, M. Alderighi, LIBERALI, VALENTINO, TARTARELLI, GIUSEPPE FRANCESCO, RAGUSA, FRANCESCO.

► JCV is a small, naked tumor polyomavirus with an icosahedral capsids containing a circular, double-stranded DNA genome. Its genome is divided into early and late…
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▼ JCV is a small, naked tumor polyomavirus with an icosahedral capsids containing a circular, double-stranded DNA genome. Its genome is divided into early and late genes, separated by a non-coding control region (NCCR) containing the promoter, the origin of replication (ORI) and the enhancer elements. Early genes encode for large T antigen, small t antigen and three different T’ proteins called T’135, T’136 and T’165. Late genes encode for the structural proteins VP1, VP2 and VP3, and the non-structural agnoprotein. JCV only replicates in human. In non-permissive cells, they are not able to support viral replication or expression of late genes. In those cells, only the transcription of early genes is observed, such as large T antigen. This leads to genome instability and inactivation of oncosoppressor proteins and eventually tumorigenesis. Cells derived from a murine brain tumor induced by JCV injection have shown different resistance to ionizing radiation. We cultured these BSB8-RR cells and characterized them comparing to the radiation sensitive BSB8 cells. Using MTT assay we showed a resistance to radiation to these cells, compare to the BSB8. We then performed cell-cycle analysis, colony formation assay e soft agar growth assay and we showed that BSB8-RR grow faster and they are more tumorigenic. Since we saw a decrease in the level of large T antigen expression in BSB8-RR, compared to BSB8, we hypothesized an involvement of large T antigen in DNA repair. Using DNA repair assays such as NHEJ and homologous recombination, we suggested that BSB8-RR cells may be resistant to radiation because they have increased homologous recombination activity, compared to the BSB8 cells. We suggested that this increase is due to the lower expression of large T antigen in BSB8-RR, that has been previously reported as inhibitor of homologous recombination. In conclusion, our data showed a more aggressive phenotype of BSB8-RR cells and a resistance to radiation that we suggested is due to the lower level of large T antigen in these cells, compared to BSB8.
Advisors/Committee Members: tutor: N. Basilico, co-tutor: D. Taramelli, I.K. Sariyer, coordinatore: R. Ghidoni, GHIDONI, RICCARDO.

► We performed ab-initio Particle-In-Cell (PIC) simulations of a pulsar magnetosphere. We injected particles in two ways: everywhere and only near to the star surface. Then…
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▼ We performed ab-initio Particle-In-Cell (PIC) simulations of a pulsar magnetosphere. We injected particles in two ways: everywhere and only near to the star surface. Then we study how the magnetosphere transitions from the vacuum to a nearly force-free configuration. We compare the injection from the surface force-free like configuration with ones obtained in a PIC simulation where particles are injected everywhere as well as with macroscopic force-free simulations. We found that although both PIC solutions have similar structure of electromagnetic fields and current density distributions, they have different particle density distribution. In fact in the injection from the surface solution, electrons and positrons counterstream only along parts of the return current regions and most of the particles leave the magnetosphere without returning to the star. We also found that pair production in the outer magnetosphere is not critical for filling the whole magnetosphere with plasma. We study how the current density distribution supporting the global electromagnetic configuration is formed by analyzing particle trajectories. We found that electrons precipitate to the return current layer inside the light cylinder and positrons precipitate to the current sheet outside the light cylinder by crossing magnetic field lines contributing to the charge density distribution required by the global electrodynamics. Moreover, there is a population of electrons trapped in the region close to the Y-point. On the other hand the most energetic positrons are accelerated close to the Y-point. These processes can have observational signatures that, with further modeling efforts, would help to distinguish this particular magnetosphere configuration from others.
Advisors/Committee Members: supervisore: P. M. Pizzochero, supervisore esterno: A. K. Harding (NASA GSFC), PIZZOCHERO, PIERRE MASSIMO.

The unprecedented and quickly increasing popularity of Online Social Networks (OSNs) is evidenced by the huge number of users who are turning to Facebook, Twitter and other social networks. The rapid growth of these…